DESCRIPTION: This revised renewal application proposes research on techniques for improving quantitative images of tumors in the breast and thorax with positron volume imaging (PVI) and single photon emission computed tomography (SPECT). The proposal focuses on new corrections for scatter and attenuation, and is motivated by the increased image accuracy and precision required for reliable tumor detection and staging, therapy planning and monitoring response to therapy. Specific clinical research projects are used to define quantitative goals. These applications include tumor imaging in the breast and torso with PVI using [F-18]-estradiol, [F-18]DG and [C-11]- thymidine, and single photon techniques using [Tc-99m]-labeled sestamibi. The work builds upon previous investigations of scatter in PVI and of energy-based scatter corrections for Tc-99m, TI-20l, I-131, and In-111. As part of that effort, a Simulation System for Emission Tomography (SimSET) was developed. This Monte Carlo-based software package tracks photons through complex heterogeneous objects and models the effects of collimation and detection. Substantial improvements in efficiency are realized by importance sampling. Although SimSET is already an indispensable research tool, several extensions are required to produce the more accurate and realistic simulations required for the work proposed. As they are developed, these extensions will be added to the package freely distributed to investigators who use SimSET for their research at other laboratories. Specifically, the proposed research will investigate: 1) new scatter corrections for PVI that incorporate energy information and coincidences detected outside the patient into a single scatter model: 2) the impact of polarization on scatter and scatter correction in PVI; 3) scatter correction techniques for singles-based transmission measurements for PVI, comparing the resulting attenuation correction to other methods that reduce attenuation measurement noise; and 4) the application of spectrum fitting techniques to 99mTc-sestamibi tumor imaging and simultaneous transmission/emission SPECT. Proposed extensions to the SimSET software will support this research by allowing more realistic and efficient collimator and detector simulations and by incorporating important physical effects such as Rayleigh scattering, polarization and positron range.